| 1. |
- Erni, W., et al.
(author)
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Technical design report for the PANDA (AntiProton Annihilations at Darmstadt) Straw Tube Tracker
- 2013
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In: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 49:2
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Journal article (peer-reviewed)abstract
- This document describes the technical layout and the expected performance of the Straw Tube Tracker (STT), the main tracking detector of the PANDA target spectrometer. The STT encloses a Micro-Vertex-Detector (MVD) for the inner tracking and is followed in beam direction by a set of GEM stations. The tasks of the STT are the measurement of the particle momentum from the reconstructed trajectory and the measurement of the specific energy loss for a particle identification. Dedicated simulations with full analysis studies of certain proton-antiproton reactions, identified as being benchmark tests for the whole PANDA scientific program, have been performed to test the STT layout and performance. The results are presented, and the time lines to construct the STT are described.
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| 2. |
- Clement, E., et al.
(author)
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Conceptual design of the AGATA 1 π array at GANIL
- 2017
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 855, s. 1-12
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Journal article (peer-reviewed)abstract
- The Advanced GAmma Tracking Array (AGATA) has been installed at the GANIL facility, Caen-France. This setup exploits the stable and radioactive heavy-ions beams delivered by the cyclotron accelerator complex of GANIL. Additionally, it benefits from a large palette of ancillary detectors and spectrometers to address in-beam γ-ray spectroscopy of exotic nuclei. The set-up has been designed to couple AGATA with a magnetic spectrometer, charged-particle and neutron detectors, scintillators for the detection of high-energy γ rays and other devices such as a plunger to measure nuclear lifetimes. In this paper, the design and the mechanical characteristics of the set-up are described. Based on simulations, expected performances of the AGATA l π array are presented.
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| 3. |
- Vogt, A., et al.
(author)
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Isomers and high-spin structures in the N=81 isotones Xe-135 and Ba-137
- 2017
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In: PHYSICAL REVIEW C. - : AMER PHYSICAL SOC. - 2469-9985. ; 95:2
-
Journal article (peer-reviewed)abstract
- The high-spin structures and isomers of the N = 81 isotones Xe-135 and Ba-137 are investigated after multinucleon-transfer (MNT) and fusion-evaporation reactions. Both nuclei are populated (i) in Xe-136+ U-238 and (ii) Xe-136+ Pb-208 MNT reactions employing the high-resolution Advanced Gamma Tracking Array (AGATA) coupled to the magnetic spectrometer PRISMA, (iii) in the Xe-136+ Pt-198 MNT reaction employing the gamma-ray array GAMMASPHERE in combination with the gas-detector array CHICO, and (iv) via a B-11+ Te-130 fusion-evaporation reaction with the HORUS gamma-ray array at the University of Cologne. The high-spin level schemes of Xe-135 and Ba-137 are considerably extended to higher energies. The 2058-keV (19/2(-)) state in Xe-135 is identified as an isomer, closing a gap in the systematics along the N = 81 isotones. Its half-life is measured to be 9.0(9) ns, corresponding to a reduced transition probability of B(E2,19/2(-) -> 15/2(-)) = 0.52(6) W.u. The experimentally deduced reduced transition probabilities of the isomeric states are compared to shell-model predictions. Latest shell-model calculations reproduce the experimental findings generally well and provide guidance to the interpretation of the new levels.
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| 4. |
- Lewandowski, Jörg, et al.
(author)
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Is the Hyporheic Zone Relevant beyond the Scientific Community?
- 2019
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In: Water. - : MDPI AG. - 2073-4441. ; 11:11
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Journal article (peer-reviewed)abstract
- Rivers are important ecosystems under continuous anthropogenic stresses. The hyporheic zone is a ubiquitous, reactive interface between the main channel and its surrounding sediments along the river network. We elaborate on the main physical, biological, and biogeochemical drivers and processes within the hyporheic zone that have been studied by multiple scientific disciplines for almost half a century. These previous efforts have shown that the hyporheic zone is a modulator for most metabolic stream processes and serves as a refuge and habitat for a diverse range of aquatic organisms. It also exerts a major control on river water quality by increasing the contact time with reactive environments, which in turn results in retention and transformation of nutrients, trace organic compounds, fine suspended particles, and microplastics, among others. The paper showcases the critical importance of hyporheic zones, both from a scientific and an applied perspective, and their role in ecosystem services to answer the question of the manuscript title. It identifies major research gaps in our understanding of hyporheic processes. In conclusion, we highlight the potential of hyporheic restoration to efficiently manage and reactivate ecosystem functions and services in river corridors.
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| 5. |
- Lewandowski, R. A., et al.
(author)
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Implementation of Person-Centered Care: A Feasibility Study Using the WE-CARE Roadmap
- 2021
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In: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601. ; 18:5
-
Journal article (peer-reviewed)abstract
- Background: Person-Centered Care (PCC) is a promising approach towards improved quality of care and cost containment within health systems. It has been evaluated in Sweden and England. This feasibility study examines initial PCC implementation in a rehabilitation hospital for children in Poland. Methods: The WE-CARE Roadmap of enablers was used to guide implementation of PCC for patients with moderate scoliosis. A multi-disciplinary team of professionals were trained in the PCC approach and the hospital Information Technology (IT) system was modified to enhance PCC data capture. Semi-structured interviews were conducted with the nine health care professionals involved in the pilot study and three patients/parents receiving care. Transcribed data were analyzed via content analysis. Results: 51 patients and their families were treated via a PCC approach. High proportions of new PCC data fields were completed by the professionals. The professionals were able to implement the three core PCC routines and perceived benefits using the PCC approach. Patients and their families also perceived improved quality care. The WE-CARE framework enablers facilitated PCC implementation in this setting. Conclusions: This feasibility pilot study indicates that the Gothenburg PCC approach can be successfully transferred to a rehabilitation hospital in Poland with favorable perceptions of implementation by both professionals and patients/their families.
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| 6. |
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| 7. |
- McCallum, James L., et al.
(author)
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A Numerical Stream Transport Modeling Approach Including Multiple Conceptualizations of Hyporheic Exchange and Spatial Variability to Assess Contaminant Removal
- 2020
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In: Water resources research. - 0043-1397 .- 1944-7973. ; 56:3
-
Journal article (peer-reviewed)abstract
- Understanding the mechanisms and controls on contaminant removal in streams is essential in managing human and ecosystem health. The hyporheic zone (HZ) plays a key role in the removal of contaminants from streams. Often, tracer tests are implemented in conjunction with measurements of compounds to assess the removal rates of contaminants in streams. The predicted removal rates largely rely on the estimated hyporheic residence time, and hence, the chosen conceptual model of hyporheic exchange flows (HEFs) will influence the predicted removal rate. Despite this, different HEF models are generally not considered when assessing contaminant removal rates. In this paper, we present a numerical modeling approach for interpreting tracer tests to determine contaminant removal rates that allows for multiple conceptual models of HEF to be considered. We demonstrate this method by interpreting data from a conservative tracer test in conjunction with grab samples of trace organic compounds using two commonly used models of HEF: one that assumes first-order exchange between the stream and the HZ and one that considers a power law weighting of first-order exchange coefficients. For the three degrading compounds measured, guanylurea, valsartan, and diclofenac, we observed that the power law model consistently predicted higher removal rates in the stream compared to the first-order model. Variations were also observed between the removal rates estimated in the HZ. Our results highlight the importance of considering multiple conceptualizations of the HEF when assessing contaminant removal rates.
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| 8. |
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| 9. |
- Peters, S., et al.
(author)
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Reconditioning the Neurogenic Niche of Adult Non-human Primates by Antisense Oligonucleotide-Mediated Attenuation of TGFβ Signaling
- 2021
-
In: Neurotherapeutics. - : Springer Nature. - 1933-7213 .- 1878-7479. ; 18:3, s. 1963-1979
-
Journal article (peer-reviewed)abstract
- Adult neurogenesis is a target for brain rejuvenation as well as regeneration in aging and disease. Numerous approaches showed efficacy to elevate neurogenesis in rodents, yet translation into therapies has not been achieved. Here, we introduce a novel human TGFβ-RII (Transforming Growth Factor—Receptor Type II) specific LNA-antisense oligonucleotide (“locked nucleotide acid”—“NVP-13”), which reduces TGFβ-RII expression and downstream receptor signaling in human neuronal precursor cells (ReNcell CX® cells) in vitro. After we injected cynomolgus non-human primates repeatedly i.th. with NVP-13 in a preclinical regulatory 13-week GLP-toxicity program, we could specifically downregulate TGFβ-RII mRNA and protein in vivo. Subsequently, we observed a dose-dependent upregulation of the neurogenic niche activity within the hippocampus and subventricular zone: human neural progenitor cells showed significantly (up to threefold over control) enhanced differentiation and cell numbers. NVP-13 treatment modulated canonical and non-canonical TGFβ pathways, such as MAPK and PI3K, as well as key transcription factors and epigenetic factors involved in stem cell maintenance, such as MEF2A and pFoxO3. The latter are also dysregulated in clinical neurodegeneration, such as amyotrophic lateral sclerosis. Here, we provide for the first time in vitro and in vivo evidence for a novel translatable approach to treat neurodegenerative disorders by modulating neurogenesis.
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| 10. |
- Schaper, Jonas L., et al.
(author)
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Hyporheic Exchange Controls Fate of Trace Organic Compounds in an Urban Stream
- 2018
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In: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 52:21, s. 12285-12294
-
Journal article (peer-reviewed)abstract
- First-order half-lives for 26 trace organic (TrOCs) were determined in the hyporheic zone (HZ) and along a 3 km reach of a first-order stream in m South Australia during both dry and wet seasons. Two salt in-stream tracer experiments were conducted and evaluated using a transient storage model to characterize seasonal differences in stream residence time and transient storage. Lagrangian and time-integrated surface water sampling were conducted to calculated half-lives in the surface water. Half-lives in the were calculated using porewater samples obtained from a modified mini-point sampler and hyporheic residence times measured via active heat-pulse sensing. Half of the investigated TrOCs (e.g., oxazepam, olmesartan, candesartan) were not significantly removed along both the investigated river stretch and the sampled hyporheic flow paths. The remaining TrOCs (e.g., metformin, guanylurea, valsartan) were found to be significantly removed in the HZ and along the river stretch with relative removals in the HZ correlating to reach-scale relative removals. Using the modeled transport parameters, it was estimated that wet season reach-scale removal of TrOCs was predominately caused by removal in the HZ when the intensity of hyporheic exchange was also higher. Factors that increase HZ exchange are thus likely to promote in-stream reactivity of TrOCs.
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| 11. |
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| 12. |
- Zhang, Haofei, et al.
(author)
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Monoterpenes are the largest source of summertime organic aerosol in the southeastern United States
- 2018
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 115:9, s. 2038-2043
-
Journal article (peer-reviewed)abstract
- The chemical complexity of atmospheric organic aerosol (OA) has caused substantial uncertainties in understanding its origins and environmental impacts. Here, we provide constraints on OA origins through compositional characterization with molecular-level details. Our results suggest that secondary OA (SOA) from monoterpene oxidation accounts for approximately half of summertime fine OA in Centreville, AL, a forested area in the southeastern United States influenced by anthropogenic pollution. We find that different chemical processes involving nitrogen oxides, during days and nights, play a central role in determining the mass of monoterpene SOA produced. These findings elucidate the strong anthropogenic–biogenic interaction affecting ambient aerosol in the southeastern United States and point out the importance of reducing anthropogenic emissions, especially under a changing climate, where biogenic emissions will likely keep increasing.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Crivello, M., et al.
(author)
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Vascular regression precedes motor neuron loss in the FUS (1-359) ALS mouse model
- 2019
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In: Disease Models and Mechanisms. - : Company of Biologists Ltd. - 1754-8403 .- 1754-8411. ; 12:8
-
Journal article (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS) presents a poorly understood pathogenesis. Evidence from patients and mutant SOD1 mouse models suggests vascular damage may precede or aggravate motor dysfunction in ALS. We have previously shown angiogenin (ANG) treatment enhances motor neuron survival, delays motor dysfunction and prevents vascular regression in the SOD1G93A ALS model. However, the existence of vascular defects at different stages of disease progression remains to be established in other ALS models. Here, we assessed vascular integrity in vivo throughout different disease stages, and investigated whether ANG treatment reverses vascular regression and prolongs motor neuron survival in the FUS (1-359) mouse model of ALS. Lumbar spinal cord tissue was collected from FUS (1-359) and non-transgenic control mice at postnatal day (P)50, P90 and P120. We found a significant decrease in vascular network density in lumbar spinal cords from FUS (1-359) mice by day 90, at which point motor neuron numbers were unaffected. ANG treatment did not affect survival or counter vascular regression. Endogenous Ang1 and Vegf expression were unchanged at P50 and P90; however, we found a significant decrease in miRNA 126 at P50, indicating vascular integrity in FUS mice may be compromised via an alternative pathway. Our study demonstrates that vascular regression occurs before motor neuron degeneration in FUS (1-359) mice, and highlights that heterogeneity in responses to novel ALS therapeutics can already be detected in preclinical mouse models of ALS.
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| 18. |
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| 19. |
- Höhne, Anja, et al.
(author)
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Fate of trace organic compounds in the hyporheic zone : Influence of microbial metabolism
- 2022
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In: Water Research. - : Elsevier BV. - 0043-1354 .- 1879-2448. ; 224
-
Journal article (peer-reviewed)abstract
- The hyporheic zone (HZ) is considered a hydrodynamically-driven bioreactor with significant pollutant removal capacities and can therefore not only improve wholestream water quality but also preserve human and ecosystem health. Microbial metabolism is hypothesized to play a key role in pollutant transformation in hyporheic sediments of natural streams. However, previous work investigating the influence of microbial metabolism on pollutant transformation has been predominantly laboratory studies. The key challenge for field studies is the appropriate determination of net microbial metabolism, i.e. information on the actual exposure times to specific microbial processes in the investigated system. The present study uses reactive fluorescent tracers to determine microbial metabolism and ultimately its influence on pollutant transformation, e.g. for trace organic compounds, in hyporheic sediments under natural conditions. In particular, the reactive fluorescent tracers resazurin and its main transformation product resorufin were used to determine the microbial metabolism of facultative or obligate aerobes. The influence of the derived microbial metabolism on the transformation of 20 trace organic compounds, such as pharmaceuticals, including 3 parent–daughter pairs, was examined. The present findings validate laboratory results on the microbially-mediated transformation of the anticonvulsant gabapentin to its main transformation product gabapentin lactam under natural conditions. All other TrOCs investigated did not show a clear link between TrOC reactivity to the microbial metabolism informed by the resazurin–resorufin-system. Overall, the present study not only demonstrates the use of the fluorescent tracer-system resazurin and resorufin for determining microbial metabolism of facultative or obligate aerobes but also generally highlights the potential of reactive fluorescent tracers to disentangle specific reactive properties and ultimately their influence on the fate of pollutants in natural HZs.
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| 20. |
- Jaeger, Anna, et al.
(author)
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Time Series of Electrical Conductivity Fluctuations Give Insights Into Long-Term Solute Transport Dynamics of an Urban Stream
- 2023
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In: Water resources research. - : American Geophysical Union (AGU). - 0043-1397 .- 1944-7973. ; 59:7
-
Journal article (peer-reviewed)abstract
- Artificial tracers are often used for quantitative estimates of solute transport properties in rivers. However, single-injection tracer tests give insights in transport characteristics limited to the ecohydrological conditions at the testing time. Series of time-consuming and laborious tracer tests would be required to properly capture seasonal changes. The present study uses intrinsic diurnal fluctuations of electrical conductivity (EC) caused by discharge of treated wastewater as a tracer to evaluate solute transport processes along a 4.7-km reach of the River Erpe, Germany. By reproducing the fluctuations recorded along the river using the solute transport model one-dimensional transport with inflow and storage, this study investigated the long-term dynamics in solute transport properties. Individual 48-hr curves of EC were used in the steady state configuration of the model to gain 48-hr-integrated estimates of selected transport parameters. Using a sliding window approach in 1-hr steps along the 2,270-hr time series of EC the temporal variability of solute transport between April and June 2016 was assessed. To test the identifiability of parameters using the proposed method, sensitivity analyses and a breakthrough curve analysis of selected 48-hr windows were implemented. With time advancing into the summer, a significant rising trend (Mann-Kendall test p-value < 0.05) of the cross sectional area of the channel was observed and attributed to the growth of macrophytes and a significant slightly decreasing trend for the storage rate was found. The presented method is of high value for river management, as promoting transient storage enhances biogeochemical cycling and benefits water quality.
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| 21. |
- Jaeger, Anna, et al.
(author)
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Transformation of organic micropollutants along hyporheic flow in bedforms of river-simulating flumes
- 2021
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
-
Journal article (peer-reviewed)abstract
- Urban streams receive increasing loads of organic micropollutants from treated wastewaters. A comprehensive understanding of the in-stream fate of micropollutants is thus of high interest for water quality management. Bedforms induce pumping effects considerably contributing to whole stream hyporheic exchange and are hotspots of biogeochemical turnover processes. However, little is known about the transformation of micropollutants in such structures. In the present study, we set up recirculating flumes to examine the transformation of a set of micropollutants along single flowpaths in two triangular bedforms. We sampled porewater from four locations in the bedforms over 78 days and analysed the resulting concentration curves using the results of a hydrodynamic model in combination with a reactive transport model accounting for advection, dispersion, first-order removal and retardation. The four porewater sampling locations were positioned on individual flowpaths with median solute travel times ranging from 11.5 to 43.3 h as shown in a hydrodynamic model previously. Highest stability was estimated for hydrochlorothiazide on all flowpaths. Lowest detectable half-lives were estimated for sotalol (0.7 h) and sitagliptin (0.2 h) along the shortest flowpath. Also, venlafaxine, acesulfame, bezafibrate, irbesartan, valsartan, ibuprofen and naproxen displayed lower half-lives at shorter flowpaths in the first bedform. However, the behavior of many compounds in the second bedform deviated from expectations, where particularly transformation products, e.g. valsartan acid, showed high concentrations. Flowpath-specific behavior as observed for metformin or flume-specific behavior as observed for metoprolol acid, for instance, was attributed to potential small-scale or flume-scale heterogeneity of microbial community compositions, respectively. The results of the study indicate that the shallow hyporheic flow field and the small-scale heterogeneity of the microbial community are major controlling factors for the transformation of relevant micropollutants in river sediments.
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| 22. |
- Jung, Christian, et al.
(author)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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In: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
-
Journal article (peer-reviewed)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 23. |
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| 24. |
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| 25. |
- Lloyd, H. M., et al.
(author)
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Supporting Innovative Person-Centred Care in Financially Constrained Environments: The WE CARE Exploratory Health Laboratory Evaluation Strategy
- 2020
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In: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601. ; 17:9
-
Journal article (peer-reviewed)abstract
- The COST CARES project aims to support healthcare cost containment and improve healthcare quality across Europe by developing the research and development necessary for person-centred care (PCC) and health promotion. This paper presents an overview evaluation strategy for testing 'Exploratory Health Laboratories' to deliver these aims. Our strategy is theory driven and evidence based, and developed through a multi-disciplinary and European-wide team. Specifically, we define the key approach and essential criteria necessary to evaluate initial testing, and on-going large-scale implementation with a core set of accompanying methods (metrics, models, and measurements). This paper also outlines the enabling mechanisms that support the development of the "Health Labs" towards innovative models of ethically grounded and evidenced-based PCC.
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| 26. |
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| 27. |
- Peralta-Maraver, Ignacio, et al.
(author)
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Environmental filtering and community delineation in the streambed ecotone
- 2018
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
-
Journal article (peer-reviewed)abstract
- A current controversy in ecology is whether biological communities are discrete biological entities or simply study units created for convenience; a debate that becomes even more heated when delimiting communities along ecotones. Here, we report an interdisciplinary study designed to address the interplay between environmental drivers and community ecology in a typical ecotone ecosystem: the streambed. Environmental filtering at a micro-scale determined how diversity, productivity and composition of the whole streambed assemblage varied with depth and with the direction of vertical water exchange. Biomass and production decreased with increasing depth, and were lower under upwelling than downwelling conditions. However, the rate at which biomass and production decreased with increasing depth differed significantly for different taxonomic groups. Using quantitative biocenosis analysis, we also showed that benthic and hyporheic zone assemblages (assemblages in close juxtaposition) could be clearly distinguished as discrete communities with individual integrity. Vertical hydrodynamic conditions also influenced the demarcation between both communities; the benthic community reached greater depths in downwelling than in upwelling zones.
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| 28. |
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| 29. |
- Schaper, Jonas L., et al.
(author)
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Fate of Trace Organic Compounds in the Hyporheic Zone : Influence of Retardation, the Benthic Biolayer, and Organic Carbon
- 2019
-
In: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 53:8, s. 4224-4234
-
Journal article (peer-reviewed)abstract
- The fate of 28 trace organic compounds (TrOCs) was investigated in the hyporheic zone (HZ) of an urban lowland river in Berlin, Germany. Water samples were collected hourly over 17 h in the river and in three depths in the HZ using minipoint samplers. The four relatively variable time series were subsequently used to calculate first order removal rates and retardation coefficients via a one-dimensional reactive transport model. Reversible sorption processes led to substantial retardation of many TrOCs along the investigated hyporheic flow path. Some TrOCs, such as dihydroxy-carbamazepine, O-desmethylvenlafaxine, and venlafaxine, were found to be stable in the HZ. Others were readily removed with half-lives in the first 10 cm of the HZ ranging from 0.1 +/- 0.01 h for iopromide to 3.3 +/- 0.3 h for tramadol. Removal rate constants of the majority of reactive TrOCs were highest in the first 10 cm of the HZ, where removal of biodegradable dissolved organic matter was also the highest. Because conditions were oxic along the top 30 cm of the investigated flow path, we attribute this finding to the high microbial activity typically associated with the shallow HZ. Frequent and short vertical hyporheic exchange flows could therefore be more important for reach-scale TrOC removal than long, lateral hyporheic flow paths.
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| 30. |
- Schuermans, Art, et al.
(author)
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Birth Weight Is Associated With Clonal Hematopoiesis of Indeterminate Potential and Cardiovascular Outcomes in Adulthood
- 2023
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In: Journal of the American Heart Association. - 2047-9980. ; 12:13
-
Journal article (peer-reviewed)abstract
- BACKGROUND: High and low birth weight are independently associated with increased cardiovascular disease risk in adulthood. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related clonal expansion of hematopoietic cells with preleu-kemic somatic mutations, predicts incident cardiovascular disease independent of traditional cardiovascular risk factors. Whether birth weight predicts development of CHIP later in life is unknown. METHODS AND RESULTS: A total of 221 047 adults enrolled in the UK Biobank with whole exome sequences and self-reported birth weight were analyzed. Of those, 22 030 (11.5%) had low (<2.5 kg) and 29 292 (14.7%) high birth weight (>4.0 kg). CHIP prevalence was higher among participants with low (6.0%, P=0.049) and high (6.3%, P<0.001) versus normal birth weight (5.7%, ref.). Multivariable-adjusted logistic regression analyses demonstrated that each 1-kg increase in birth weight was associated with a 3% increased risk of CHIP (odds ratio, 1.03 [95% CI, 1.00–1.06]; P=0.04), driven by a stronger association ob-served between birth weight and DNMT3A CHIP (odds ratio, 1.04 per 1-kg increase [95% CI, 1.01–1.08]; P=0.02). Mendelian randomization analyses supported a causal relationship of longer gestational age at delivery with DNMT3A CHIP. Multivariable Cox regression demonstrated that CHIP was independently and additively associated with incident cardiovascular disease or death across birth weight groups, with highest absolute risks in those with CHIP plus high or low birth weight. CONCLUSIONS: Higher birth weight is associated with increased risk of developing CHIP in midlife, especially DNMT3A CHIP. These findings identify a novel risk factor for CHIP and provide insights into the relationships among early-life environment, CHIP, cancer, and cardiovascular disease.
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| 31. |
- Swedberg, Karl, 1944, et al.
(author)
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Testing cost containment of future healthcare with maintained or improved quality—The COSTCARES project
- 2021
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In: Health Science Reports. - : Wiley. - 2398-8835. ; 4:2
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Research review (peer-reviewed)abstract
- Background: Increasing healthcare costs need to be contained in order to maintain equality of access to care for all EU citizens. A cross-disciplinary consortium of experts was supported by the EU FP7 research programme, to produce a roadmap on cost containment, while maintaining or improving the quality of healthcare. The roadmap comprises two drivers: person-centred care and health promotion; five critical enablers also need to be addressed: information technology, quality measures, infrastructure, incentive systems, and contracting strategies. Method: In order to develop and test the roadmap, a COST Action project was initiated: COST−CARES, with 28 participating countries. This paper provides an overview of evidence about the effects of each of the identified enablers. Intersections between the drivers and the enablers are identified as critical for the success of future cost containment, in tandem with maintained or improved quality in healthcare. This will require further exploration through testing. Conclusion: Cost containment of future healthcare, with maintained or improved quality, needs to be addressed through a concerted approach of testing key factors. We propose a framework for test lab design based on these drivers and enablers in different European countries.
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| 32. |
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| 33. |
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